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Structural analysis of DNA-PKcs: modelling of the repeat units and insights into the detailed molecular architecture.

Abstract：

:DNA-dependent protein kinase (DNA-PK) is part of the eukaryotic DNA double strand break repair pathway and as such is crucial for maintenance of genomic stability, as well as for V(D)J (variable-diversity-joining) recombination. The catalytic subunit of DNA-PK (DNA-PKcs) belongs to the phosphatidylinositol-3 (PI-3) kinase-like kinase (PIKK) superfamily and is comprised of approximately 4100 amino acids. We have used a novel repeat detection method to analyse this enormous protein and have identified two different types of helical repeat motifs in the N-terminal region of the sequence, as well as other previously unreported features in this repeat region. A comparison with the ATMs, ATRs, and TORs show that the features identified are likely to be conserved throughout the PIKK superfamily. Homology modelling of parts of the DNA-PKcs sequence has been undertaken and we have been able to fit the models to previously obtained electron microscopy data. This work provides an insight into the overall architecture of the DNA-PKcs protein and identifies regions of interest for further experimental studies.

journal_name

J Struct Biol

journal_title

Journal of structural biology

authors

Brewerton SC,Doré AS,Drake AC,Leuther KK,Blundell TL

doi

10.1016/j.jsb.2003.11.024

keywords:

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

295-306

issue

3

eissn

1047-8477

issn

1095-8657

pii

S1047847703002971

journal_volume

145

pub_type

杂志文章

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